Systems Analysis and Improvement to Optimize pMTCT: A Cluster Randomized Trial. Despite significant increases in global health investment and the availability of low-cost, efficacious interventions designed to reduce mother to child HIV transmission in low and middle income countries with high HIV burden, the translation of these scientific advances into effective delivery strategies has been slow, uneven and incomplete. As a result, pediatric HIV infection remains largely uncontrolled. Enhancing the implementation of pMTCT interventions through contextually appropriate systems analysis and improvement approaches can potentially reduce drop-offs along the pMTCT cascade, leading to dramatic improvements in infant and maternal outcomes. The goal of this proposal is to develop a model for systematic assessment and improvement of pMTCT services in sub-Saharan Africa. In specific aim 1, we will identify health system factors and service delivery approaches associated with high and low performing pMTCT services in Cote d'Ivoire, Kenya and Mozambique. In specific aim 2 we will adapt evaluate the feasibility and impact of a systems analysis tool and associated performance enhancement approach for pMTCT services in Cote d'Ivoire, Kenya and Mozambique. This systems analysis tool and associated performance enhancement approach is currently being developed and piloted for pMTCT services in Mozambique. The results of this implementation research are expected to generate knowledge of global health significance, and by disseminating the study results and intervention tools through the broad PEPFAR network, can rapidly impact pMTCT service delivery enhancements across the highest need countries. PUBLIC HEALTH RELEVANCE: This research is highly relevant to public health in developing countries, where implementation of health advancements has not reached populations with sufficient speed and scale. Through assessing whether the application of systems engineering approaches leads to improvements in pMTCT effectiveness in Cote d'Ivoire, Kenya and Mozambique, we will build evidence on how to achieve rapid, sustainable and scalable improvements in services that can dramatically improve population health measures in resource limited countries.